tbuckley/cabot-search huggingface dataset:
POSTER ABSTRACTSP01 Our experience with outpatient initiation of propranolol in the treatment of complicated infantile haemangiomas
Authors: Paula Finnegan, Siobhán Rafferty, Berbie Byrne, Ashling O’Shaughnessy, Maeve Lynch
Journal: British Journal of Dermatology (2023)

Abstract During the COVID-19 pandemic, consensus expert opinion published guidelines on the outpatient initiation of propranolol in the treatment of complicated infantile haemangiomas (IH). We performed an audit from 2015 to 2019 which demonstrated that the establishment of a dedicated IH clinic both improved access to and resulted in earlier initiation of propranolol in the Mid-West region. The aims of this re-audit were to evaluate patients referred to our clinic with IH, and to assess our compliance with international guidelines on the use of propranolol for the treatment of IH. All patients commenced on propranolol following referral to our dedicated IH clinic from January 2019 to September 2021 were identified from our dermatology database, and clinical and demographic data were collected from their charts. Data analysis demonstrated a 21-fold increase in outpatient initiation of propranolol, with 57% (n = 16/28) of patients commencing treatment as outpatients. In those patients who received inpatient initiation of propranolol, inpatient initiation was indicated in 88% (n = 8/9). We report treatment of 28 patients over 2 years with IH, 16 of whom were safely initiated in the outpatient setting, consistent with updated international guidelines. The main focus should now be on primary care education about IH in our community to ensure early intervention with propranolol when indicated.
P17 <i>Pseudomonas</i> infection causing acute painful flexural exacerbation in a child with IFAP syndrome
Authors: Karina Forde, Conor Broderick, Natasha Stembridge, Gabriela Petrof, Nigel Burrows
Journal: British Journal of Dermatology (2023)

Abstract Ichthyosis follicularis alopecia and photophobia (IFAP) syndrome is a rare, X-linked inherited disorder caused by pathogenic mutations in the MBTPS2 gene. Seventy cases have been reported previously. The phenotypic spectrum varies, but IFAP consistently causes noninflammatory follicular keratoses, nonscarring alopecia and progressive corneal scarring. A 7-year-old boy, with IFAP syndrome associated with neurodevelopmental delay, chorioretinal coloboma and poor growth requiring gastrostomy, presented with a 4-week history of worsening flexural erythema and pain. Trials of topical steroids with fucidic acid, nystatin and oral penicillin had proven ineffective. On initial evaluation he had florid painful flexural erythema with surrounding crusting and scale. The Nikolsky sign was negative. He was systemically unwell with fever, dehydration and malaise requiring hospital admission. Laboratory evaluation demonstrated leucocytosis with neutrophilia and peak CRP of 100. He was treated empirically for bacterial superinfection including Staphylococcus scalded skin syndrome with intravenous clindamycin. With no appreciable improvement after 48 h, antimicrobial therapy was extended to include fluconazole and aciclovir. After 5 days, he continued to be febrile and systemically unwell with extensive yellow-brown crusting most marked at the flexural areas, and clindamycin was switched to piperacillin/tazobactam to provide antipseudomonal coverage. Skin swab cultures subsequently confirmed heavy growth of Pseudomonas aeruginosa. Within 48 h there was marked clinical improvement. He was discharged home to complete a course of oral antibiotics. This case highlights the importance of early consideration of Pseudomonas infection as a cause of subacute flexural exacerbations, particularly in those with skin barrier abnormalities, including inherited ichthyoses.
P14 Blueberry muffin syndrome secondary to acute myeloid leukaemia: a learning point
Authors: Veronica Melchionda, Inge Kreuser-Genis, Tess McPherson
Journal: British Journal of Dermatology (2023)

Abstract A baby was initially referred at 6 weeks developing multiple erythematous, bruise-like and light-brown subdermal lumps over the head, face, arms, legs and buttocks. She had been born following breech presentation by elective C-section, which had been complicated by trauma and blood loss. No other clinical concerns were raised at this time. Nonaccidental injury was considered; however, subcutaneous fat necrosis of the newborn was the diagnosis made by paediatric team following slightly raised calcium and suggestive ultrasounds features. Newer lesions continued to arise in the same areas over 6 weeks, now with difficulty in feeding and irritability. One small cervical lymph node could be palpated. This was atypical for subcutaneous fat necrosis of the newborn and an urgent dermatological option was sought. On review, the lesions were clinically in keeping with an infiltrative process (blueberry muffin syndrome) and an urgent skin biopsy, blood film and TORCH screen were requested. A 4-mm punch biopsy confirmed leukaemia cutis with evidence of myeloid differentiation. MLL (KMT2A) rearrangement was detected, which was also subsequently found on a bone marrow sample. A peripheral blood film identified a population for NG2-positive myeloid blasts (6%), raising the possibility of infant acute myeloid leukaemia (AML). A TORCH screen did not highlight any congenital infections. The baby was promptly commenced on chemotherapy for AML. This case highlights how presentation can be atypical, the importance of reviewing possible diagnoses and considering an early biopsy to enable prompt treatment if required.
P1306: IMPACT OF HLA DISPARITY ON THE RISK OF OVERALL MORTALITY IN PATIENTS WITH EXTENSIVE CHRONIC GVHD
Authors: Shigeo Fuji, Akitoshi Hakoda, Junya Kanda, Takahiro Fukuda, Noriko Doki, Yuta Katayama, Naoyuki Uchida, Yukiyasu Ozawa, Yoshinobu Kanda, Masatsugu Tanaka, Keisuke Kataoka, Takahide Ara, Masashi Sawa, Makoto Onizuka, Yasushi Onishi, Takafumi Kimura, Tatsuo Ichinohe, Yoshiko Atsuta, Ayumi Shintani, Satoko Morishima
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Chronic graft-versus-host disease (cGVHD) is a significant cause of morbidity and mortality in long-term survivors after allogeneic hematopoietic cell transplantation (allo-HCT). It is unclear whether stem cell source or HLA disparity significantly impact the overall survival (OS) after the development of extensive cGVHD. Aims: The aim of this study is to clarify the impact of HLA disparity on the clinical outcome after the development of extensive cGVHD. Methods: We performed a retrospective analysis using a database of the Japanese Society for Transplantation and Cellular Therapy. This retrospective study included patients who underwent their first allo-HCT between 2007 and 2016 and subsequently developed extensive cGVHD. The data was obtained from the Transplant Registry Unified Management Program of Japanese Society for Transplantation and Cellular Therapy. Results: We analyzed the clinical outcomes of 4,389 patients who developed extensive cGVHD. The median age of the patients was 48 years (IQR 34–58). The probability of 2-year OS after the onset of extensive cGVHD in the study cohort was 68.3% (95% CI 66.9–69.8). The multivariate analysis showed that the presence of HLA disparity ≥2 loci in the related HCT was associated with an inferior OS (HR 1.68, 95% CI 1.11–2.52, P=0.014, Figure), but there was no impact of HLA disparity in unrelated HCT and cord blood transplantation (CBT). The cumulative incidence of 2-year NRM after the onset of extensive cGVHD was 18.5% (95% CI, 17.2-19.8). In multivariate analysis, there was a trend toward a higher NRM rate in patients with HLA disparity ≥2 loci in related HCT, but there was no significant impact of HLA disparity in unrelated HCT and CBT.Summary/Conclusion: Our study suggests that HLA disparity could be a prognostic factor in the related HCT but not in the unrelated HCT or CBT in patients with extensive cGVHD. Further research using other databases is necessary to confirm our findings. Keywords: Graft-versus-host disease (GVHD), Allogeneic hematopoietic stem cell transplant
Tumor immunogenicity dictates reliance on TCF1 in CD8+ T cells for response to immunotherapy
Authors: Giulia Escobar, Katherine Tooley, Joan Pagès Oliveras, Linglin Huang, Hanning Cheng, Michelle L. Bookstaver, Camilla Edwards, Eugene Froimchuk, Chang Xue, Davide Mangani, Rajesh K. Krishnan, Natanael Hazel, Carola Rutigliani, Christopher M. Jewell, Luca Biasco, Ana C. Anderson
Journal: Cancer Cell (2023)
PB2637: OUR EXPERIENCE WITH AVATROMBOPAG TREATMENT IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA
Authors: Libor Cervinek
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: The treatment of immune thrombocytopenia has undergone major changes in recent years. Long-term corticoid therapy or splenectomy were abandoned. As part of second-line treatment, thrombopoietin receptor agonists are the essential drugs. New orally administered drug avatrombopag, was added to the previously used romiplostim and eltrombopag. Aims: In our poster, we present 20 patients aged ≥ 18 years with a diagnosis of primary immune thrombocytopenia treated with avatrombopag at our Department since April 2022. Methods: Data on patient characteristics, disease history, treatment pathways, response to treatment and adverse events (AEs) were collected from medical records (observation period from date of ITP diagnosis to data collection - December 2022). (Tabel 1.) Results: 11 patients are complete responders (CR), 6 partial responders and 3 patients non responders. 9 patients received avatrombopag as the first TPO receptor agonist. Average daily dose in our set of patients is 20 mg (1 tablet). The vast majority take one tablet daily, while one of them receive avatrombopag in higher dose and on the other side there are some of them on less frequent regimen (up to once weekly). Patients in this pool may take and advantage of peroral use with no food restrictions, no liver harm even in cirrhotic/CLD patients. In group of responders, we observed a rapid onset of effect on platelet levels, approximately 2 weeks. Summary/Conclusion: Our data confirm very good therapeutic effectiveness with a minimum of side effects. Table 1Keywords: Immune thrombocytopenia (ITP)
PB2375: PLTP REGULATES BCR SIGNALING AND TUMOR MICROENVIRONMENT IN DIFFUSE LARGE B-CELL LYMPHOMA THROUGH REPROGRAMMING OF LIPID METABOLISM ENVIRONMENT
Authors: Wenyu Shi
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma (NHL). While approximately 60% of patients can be cured using the standard R-CHOP regimen of chemotherapy, around 40% still die due to relapse or refractory disease. Therefore, it is necessary to explore new molecular mechanisms of DLBCL to find targets for more precise treatment. Reprogramming of lipid metabolism is closely related to a variety of tumor processes, including DLBCL. However, phospholipid transfer protein (PLTP), which is highly relevant to lipid metabolism, has not been previously reported in lymphoma. Aims: This project aims to investigate the specific mechanisms by which PLTP regulates DLBCL. Methods: In this study, we used immunofluorescence to investigate the prognostic correlation between PLTP expression on DLBCL in tissue Microarrays. We constructed PLTP knockdown vectors and analyzed the changes in DLBCL biological activity after the decrease of PLTP expression from in vivo and in vitro. We verified the specific mechanism of action of PLTP on cholesterol changes by mass spectrometry sequencing, cholesterol content assay, and Co-IP assay. We analyzed the alteration of the corresponding BCR signaling pathway after knocking down PTLP resulting in reduced cholesterol accumulation by GSEA and Western blot. What’s more, We investigated the effect of knocking down PLTP on macrophages in the DLBCL microenvironment with the help of single-cell sequencing and multilabel immunofluorescence Results: Our group found that PLTP was highly expressed in DLBCL and was associated with poor prognosis. Knockdown of PLTP inhibited tumor cell line survival and alleviated tumor progression in mice, especially in the ABC subtype. Inhibition of PLTP led to a reduction in cholesterol accumulation and thus attenuated lipid raft-mediated BCR signaling reducing tumor cell proliferation. The concomitant reduction in membrane cholesterol and BCR signaling may be associated with reduced cholesterol transport by ATP-binding cassette transporter A1 (ABCA1). At the same time, we found that PLTP was associated with TAMs and M2-type macrophage infiltration. PLTP-activated BCR signaling could polarize TAMs to M2 type via the SYK-STAT3-CCL2 axis, remodeling the tumor microenvironment and leading to immune escape. Summary/Conclusion: In a word, we found that high PLTP expression in DLBCL causes cholesterol accumulation, which enhances lipid raft activation of BCR signaling. On the one hand, PLTP promotes the malignant phenotype of lymphoma cells; on the other hand, it induces tumor-associated macrophage polarization to reshape the microenvironment, leading to immune escape. The results will provide a new target for the precise treatment of DLBCL from a new perspective on lipid metabolism. Keywords: B cell lymphoma
PB2665: THROMBOTIC PROFILE OF A SERIE OF 14 PATIENTS CARRYING 67ARG&gt;STOP POLYMORPHISM IN THE SERPINE A10 (PROTEASE-DEPENDENT PROTEIN Z INHIBITOR) GENE
Authors: Nuria Bermejo, Verónica Casado-Cabanillas, José María González-Valero, Víctor Higuero, Fatima Ibañez Espacio
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Serpine 10 67Arg>Stop polymorphism in the Serpine A10 (Protease-dependent Protein Z-Inhibitor, PZI) gene is associated with a PZI deficiency, which significantly increases the risk of developing venous thromboembolism (VTE). However, the general characteristics, type and predisposing factors for VTE in carriership of this polymorphism are not stablished yet. Aims: To describe the thrombotic profile observed in a small patients series carriying Serpine A10 67Arg>Stop polymorphism. Methods: We selected 14 consecutive patients referred for thrombophilia screening to our center between January 2021 and February 2023, who were identified as Serpine A10 heterocygotic carriers of 67Arg>Stop polymorphism. DNA extraction was performed, in samples obtained in EDTA, using QIAamp DNA Blood Mini Kit according to the manufacturer’s instructions (QIAGEN), and the genotyping was carried out using the ThromboInCode kit (GenInCode) in a Bio- Rad thermocycler according to the manufacturer’s specifications Results: The general characteristics, type and predisposing factors for VTE are shown in Table 1. Summary/Conclusion: In our experience, the thrombotic clinic in heterozygous carriers of the SERPINA10 67Arg>Stop variant is fundamentally recurrent lower limb DVT and isolated PE, and these patients seem to be at greater risk of developing VTE from the age of 45 and in the presence of acquired cardiovascular risk factors. Multi-centre studies with an adequate number of patients are necessary for a better characterisation of the thrombotic profile of the carriers of this polymorphism.Keywords: Thrombosis, Gene polymorphism, Inherited thrombophilia, Protein Z
PB2629: LATE DIAGNOSIS OF TWO ADULT SIBLINGS WITH BERNARD SOULIER SYNDROME (BSS)
Authors: Essam Altowyan, Andres Suarez, Zainab Al-Housni, Davide Matino, Alfonso Iorio
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Bernard Soulier Syndrome (BSS) is a rare bleeding disorder with a 1 per 1 million prevalence. Most cases are diagnosed during childhood. However, like our patient, many cases are under-recognized or misdiagnosed. Aims: To raise awareness for a rare bleeding disorder that may be misdiagnosed earlier in life. Methods: We report two siblings with a delayed diagnosis of BSS. In both, we performed the following tests: complete blood count and blood smear, coagulation profile, von Willebrand antigen, von Willebrand activity, factor VIII activity, platelet aggregation test and electron microscopy examination of platelets. Results: Two siblings were diagnosed with congenital thrombocytopenia of unknown cause with a platelet count of 40×109/L to 50×109/L. Their parents had normal platelet counts without any bleeding history. The first patient is a 21-year-old female who had heavy menstrual bleeding since menarche, requiring multiple hospitalizations. The second patient is an 18-year-old male with a life-long history of easy bruising and recurrent epistaxis requiring multiple visits to the emergency department for severe nasal bleeding. In both cases, platelet aggregation tests showed a lack of agglutination with Ristocetin. Response to the other agonists was normal. Laboratory finding is shown in table 1. We decided to manage them as follows: estrogen-containing oral contraceptive pill for menorrhagia. Tranexamic acid for mucosal bleeding. Recombinant factor VIIa (90mcg/kg) in case of severe bleeding or major surgery and consideration for platelet transfusion if the above measures did not control bleeding. Summary/Conclusion: It is essential to consider BSS within the differential diagnosis of adult patients presenting with thrombocytopenia and giant platelets in the blood smear. BSS is a rare disorder that may easily have been underdiagnosed or misdiagnosed earlier in life. The presence of chronic macrothrombocytopenia in two siblings raised suspicion for an underlying genetic condition. - Test Female 21-year-old Male 18-year-old Platelet 40 ×109/L 52 ×109/L Blood smear Giant platelets Giant platelets Coagulation profile Normal Normal Factor 8 activity 1.14 U/mL 0.94 U/mL VWF antigen 0.96 U/mL 0.79 U/mL VWF Activity 1.00 U/mL 0.68 U/mL Platelet aggregation test No response to Ristocetin No response to Ristocetin Electron microscopy platelet whole mount Normal Normal Table 1 Keywords: Platelet aggregation, Bernard-Soulier syndrome
Absence of Lugol staining indicates initiation of esophageal squamous cell carcinoma: A combined genomic and epidemiologic study
Authors: Zhen Liu, Mengfei Liu, Ying Liu, Ren Zhou, Amir Abliz, Wenqing Yuan, Chuanhai Guo, Lixin Zhang, Wei He, Hongchen Zheng, Yi Huang, Yaqi Pan, Fangfang Liu, Zhe Hu, Huanyu Chen, Hong Cai, Zhonghu He, Yang Ke
Journal: Cell Reports Medicine (2023)

The genomic characteristics during the carcinogenic process of esophageal squamous cell carcinoma (ESCC) remain largely unknown. We report here the genomic characteristics of 106 esophageal tissues of various stages from a population-based screening cohort in China ("Endoscopic Screening for Esophageal Cancer in China" trial) and 57 ESCC tissues from a local hospital. A significant increase in somatic mutation and copy number alterations is observed in the non-dysplastic Lugol unstaining lesions (ND-LULs). Extensive clonal expansion has emerged in the ND-LULs to an extent similar to that in higher-stage lesions. The burden of genomic alterations correlates with the size of LULs in the ND-LULs. 8-year follow-up shows that ND-LULs harbor an increased risk of progression to ESCC (adjusted IRR6-10 mm vs. none = 4.66, adjusted IRR>10 mm vs. none = 40.70), and the risk is correlated with LUL size for both non-dysplastic and dysplastic lesions. Lugol unstaining can be the initial stage in the carcinogenic process of ESCC.
Timing of maternal isoniazid preventive therapy on tuberculosis infection among infants exposed to HIV in low-income and middle-income settings: a secondary analysis of the TB APPRISE trial
Authors: Amita Gupta, Priya Singh, Lisa Aaron, Grace Montepiedra, Tsungai Chipato, Lynda Stranix-Chibanda, Vongai Chanaiwa, Tichaona Vhembo, Mercy Mutambanengwe, Gaerolwe Masheto, Mpho Raesi, Sarah Bradford, Amanda Golner, Diane Costello, Vandana Kulkarni, Aisa Shayo, Enid Kabugho, Patrick Jean-Phillippe, Nahida Chakhtoura, Timothy R Sterling, Gerhard Theron, Adriana Weinberg
Journal: The Lancet Child & Adolescent Health (2023)
P25 Becker naevus is associated with neurocognitive abnormalities in a substantial proportion of children
Authors: Pablo Lopez Balboa, Nicole Knoepfel, Veronica Kinsler, Satyamaanasa Polubothu
Journal: British Journal of Dermatology (2023)

Abstract Becker naevus and Becker naevus syndrome are mosaic disorders caused in 60% of cases by postzygotic variants in the gene ACTB which encodes β-actin. We observed several patients with Becker naevus and coexistent neurocognitive abnormalities and began to study this potential association. All 51 patients seen in the last 5 years with a differential diagnosis of Becker naevus in electronic and/or photographic records were identified retrospectively. Clinical notes, photographs, radiology and histopathology were reviewed. Twenty-one patients were removed due to a different or doubtful final cutaneous diagnosis. Neurocognitive diagnoses were included only when made by a clinician, all external to the Paediatric Dermatology department. All but three patients had had their neurodevelopment assessed. Nine of the 27 patients assessed (33.3%) had a neurocognitive diagnosis, and all nine were male. Two children had autistic spectrum disorder (ASD), four had attention deficit hyperactivity disorder (ADHD) and two children had both diagnoses. MRI scans had been performed in six of the nine patients, and two had abnormal findings. A very substantial proportion of this cohort of patients with a definite diagnosis of Becker naevus have an independent diagnosis of ASD or ADHD, which in line with all-cause ASD/ADHD appears to be commoner in males. This is a new description. Germline genetic disorders caused by gain- or loss-of-function variants in ACTB are associated with neurocognitive abnormalities. Genotyping is ongoing to examine any association between the neurocognitive phenotype and mosaic ACTB variants in this clinical cohort.
P19 Pemphigus foliaceus in a 13-year-old child
Authors: Maria L Bageta, John Mee, Samantha Levine, Gabriela Petrof, Anna E Martinez
Journal: British Journal of Dermatology (2023)

Abstract Pemphigus foliaceus (PF) is an autoimmune blistering disease caused by autoantibodies against desmoglein 1, which cause acantholysis and intraepithelial blisters. PF classically presents in adults and, excluding the endemic form of PF (fogo salvagem) found in North Africa, Turkey and South America, it rarely occurs in children. We present a previously fit and well 13-year-old girl who was referred with a 2-year history of multiple small blisters on the legs which gradually spread to the trunk and arms. Concomitantly she had severe abdominal pain and alternated constipation with diarrhoea. A skin biopsy suggested a diagnosis of PF. She was commenced on azathioprine which had to be subsequently discontinued due to severe muscle pain and fatigue. She has had a 15-month-course of oral prednisolone which was difficult to wean due to acute flares. A repeat biopsy showed features of pemphigus, direct immunofluorescence showed intercellular deposition of IgG and C3 in the epidermis and ELISA revealed positive autoantibodies against desmoglein 1 (110 U mL–1), in keeping with PF. She was commenced on erythromycin with small improvement and was therefore switched to azithromycin which was discontinued after 5 days due to severe abdominal pain. No abnormalities were seen on a colonoscopy and upper gastrointestinal endoscopy. Despite treatment with erythromycin and topical tacrolimus she continued experiencing acute flares, particularly over her chest and back. Dapsone 50 mg once daily was prescribed and was increased to 75 mg to fully resolve the skin lesions. She is under follow-up and her disease has now remained quiescent for a year.